title: Pathogenesis of ANCA-associated vasculitis: new possibilities for intervention.
abstract: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) comprise granulomatosis with polyangiitis (GPA), primarily associated with antibodies to proteinase 3 (PR3-ANCA); microscopic polyangiitis (MPA); and eosinophilic granulomatosis with polyangiitis (EGPA), both principally associated with antibodies to myeloperoxidase (MPO-ANCA). Genetic and environmental factors are involved in their etiopathogenesis, with a possible role for silica exposure in AAVs and Staphylococcus aureus infection in GPA. The distinct associations of PR3-ANCA and MPO-ANCA with different HLA class II antigens, which are stronger than those with the associated diseases, suggest a pathogenic role for those ANCAs and indicate that GPA and MPA are different diseases. Both in vitro and in vivo experimental data have shown that MPO-ANCA can induce necrotizing small-vessel vasculitis and glomerulonephritis. The additional role of the alternative pathway of complement activation has been demonstrated in human and experimental pathology. Also, T cells seem to be involved in lesion development, particularly in the kidney. Granuloma formation, as seen in PR3-ANCA-associated GPA, is not well explained by the presence of autoantibodies in experimental models. Here, T cells seem crucial. Recently obtained insights into the pathogenesis of AAVs have led to more targeted treatment of these life-threatening diseases.
authors.affiliation: Department of Rheumatology & Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: c.g.m.kallenberg@umcg.nl.
authors.forename: Cees G M
authors.initials: CG
authors.lastname: Kallenberg
authors.forename: Coen A
authors.initials: CA
authors.lastname: Stegeman
authors.forename: Wayel H
authors.initials: WH
authors.lastname: Abdulahad
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
mesh_terms: D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000235:genetics* / Q000276:immunology; D015267:Churg-Strauss Syndrome / Q000235:genetics* / Q000276:immunology; D003170:Complement Pathway, Alternative / Q000235:genetics / Q000276:immunology; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D055953:Microscopic Polyangiitis / Q000235:genetics* / Q000276:immunology; D053146:Myeloblastin / Q000276:immunology; D009195:Peroxidase / Q000235:genetics* / Q000276:immunology; D010488:Polyarteritis Nodosa / Q000235:genetics / Q000276:immunology; D012822:Silicon Dioxide / Q000009:adverse effects; D013203:Staphylococcal Infections / Q000150:complications / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000949:Histocompatibility Antigens Class II; D012822:Silicon Dioxide; D009195:Peroxidase; D053146:Myeloblastin
keywords: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis; antibodies to myeloperoxidase (MPO-ANCA); antibodies to proteinase 3 (PR3-ANCA); granulomatosis with polyangiitis (GPA); microscopic polyangiitis (MPA); pathogenesis